Post-Transplant Cyclophosphamide, Abatacept, and Short Course of Tacrolimus Combination (CAST) Is Safe and Seems Highly Effective in Preventing Graft-Versus-Host Disease Following Haploidentical Peripheral Blood Stem Cell Transplantation

The introduction of post-transplant cyclophosphamide (PTCy) has circumvented the need for T-cell depletion following haploidentical stem cell transplantation (SCT). By expanding the donor pool for patients from certain ethnic minorities, this has addressed to some degree an important health care disparity issue in SCT. However, a recent registry study showed increased incidence GvHD and inferior outcomes in patients receiving haploidentical SCT with PTCy, tacrolimus and mycophenolate mofetil for GvHD prevention as opposed to matched unrelated donor SCT with PTCy-based GvHD prevention. Seeking to improve the results of GvHD prevention in the setting of haploidentical SCT, we examined a combination of PTCy, abatacept and a short course of tacrolimus (CAST). Abatacept is a recombinant soluble fusion protein composed of the extracellular domain of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) fused to the Fc region of IgG1. Abatacept blocks CD28-CD80I86 axis and prevents T-cell co-stimulation. In early studies, abatacept has shown promising results when added to methotrexate and tacrolimus in matched and mismatched donor SCT. We initiated a phase Ib-II clinical trial for patients with hematological malignancies undergoing haploidentical SCT. Patients received G-CSF mobilized peripheral blood grafts from related haploidentical donors. GvHD prevention consisted of PTCy 50mg/kg IV on day +3 and +4 with forced hydration, abatacept 10mg/kg IV on day +5, +14 and +28 and tacrolimus. Tacrolimus was started on day +5 at 0.02mg/kg/day by continuous IV and adjusted thereafter to maintain a trough level of 5-12ng/mL. Tacrolimus taper was planned to begin on day +60 and complete by day +90 in the absence of GvHD. All patients received standard supportive care including levofloxacin until neutrophil engraftment, posaconazole until day +75, acyclovir for 1 year and, if CMV positive by serology, letermovir until day +100. Pneumocystis Jiroveci prophylaxis was started after neutrophil engraftment and continued until 6 months post-transplant. G-CSF was administered routinely until neutrophil engraftment. Since September 2020, 19 patients were enrolled. Three patients are too early in their post-transplant course and were excluded from this analysis. Patients' characteristics are summarized in the table. All but 2 patients received cryopreserved products. Median times to ANC and platelet engraftment were 18.5 days (14-30) and 28.5 (16-61). All 16 patients achieved full whole blood donor chimerism by day +30. There was no secondary graft failure. With a median follow-up was 149.5 days (41-308) with 10 patients having >120 days and 8 >180 days of follow-up, 4 patients developed skin acute GvHD (all grade I). No patient developed grade II-IV acute GvHD. Two patients developed skin chronic GvHD (limited, both moderate). Both cases were diagnosed following COVID-19 vaccination. Fifteen patients completed tacrolimus taper by day +90. Two patients received systemic steroids, one for treatment of cGvHD. The remaining patients required no further immunosuppressive therapy beyond day +90. CMV activation rate was 25%. One patient had EBV reactivation and required preemptive therapy with 2 weekly rituximab doses. There were no cases of adenovirus, HHV-6 virus or BK virus reactivation. Four patients developed renal insufficiency (3 in the setting of acute sepsis and 1 with thrombotic microangiopathy, which resolved after tapering off tacrolimus. One patient with adult T-cell leukemia/lymphoma relapsed and died. All other patients are alive and well. In summary, our preliminary results suggest that CAST with shortened course of tacrolimus is feasible and seems to offer very promising outcomes with low rates of acute GvHD. The study is accruing actively and the results of a larger cohort with longer follow-up will be presented at the meeting. If confirmed, by improving the outcomes of haploidentical SCT, this regimen may further address a health care disparity issue, offering almost every patient in need of allogeneic SCT an alternative donor option with equal outcomes. Figure 1 Figure 1. Disclosures Al-Homsi: Daichii Sanyko: Consultancy; Celyad: Other: Advisory Board. Abdul-Hay: Abbvie: Consultancy; Servier: Other: Advisory Board, Speakers Bureau; Jazz: Other: Advisory Board, Speakers Bureau; Takeda: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Abatacept - off label use as GvHD prevention Cyclophosphamide - off label use as GvHD prevention

A Time Series Analysis and Forecast of COVID-19 Healthcare Disparity

This work focuses on a time series analysis and forecast of COVID 19. Decision makers and medical providers will find the work useful in improving cares to the disadvantaged demography, reduce the spread of the coronavirus and improve mitigation strategy to combat the impact of the disease. Our anatomy of COVID cases spans March 2020 to December 2020. COVID 19 forecasting cases and deaths models were built for the total population and blacks in eight states in the USA. State with medium to large populations of blacks were considered for the experiment. We defined COVID-19 Health Care Disparity (CHCD) as the difference between the percentage of Black Cases to Total Cases and Black Deaths to Total Deaths within a period. We hypothesized that a disparity exists if the ratio of black cases to the total COVID-19 population in a state, is less than the ratio of black deaths to the total deaths in the same state. The outcome of our experiment shows that there exists COVID-19 Health Care Disparity in the black community. Furthermore, all things being equal, our forecast suggests that the COVID-19 Health Care Disparities will continue at least till the end of the first quarter of 2021.

An Electronic Medical Record-Derived Individualized Performance Metric to Measure Risk-Adjusted Adherence with Perioperative Prophylactic Bundles for Health Care Disparity Research and Implementation Science

Background Health care disparity persists despite vigorous countermeasures. Clinician performance is paramount for equitable care processes and outcomes. However, precise and valid individual performance measures remain elusive. Objectives We sought to develop a generalizable, rigorous, risk-adjusted metric for individual clinician performance (MIP) derived directly from the electronic medical record (EMR) to provide visual, personalized feedback. Methods We conceptualized MIP as risk responsiveness, i.e., administering an increasing number of interventions contingent on patient risk. We embedded MIP in a hierarchical statistical model, reflecting contemporary nested health care delivery. We tested MIP by investigating the adherence with prophylactic bundles to reduce the risk of postoperative nausea and vomiting (PONV), retrieving PONV risk factors and prophylactic antiemetic interventions from the EMR. We explored the impact of social determinants of health on MIP. Results We extracted data from the EMR on 25,980 elective anesthesia cases performed at Penn State Milton S. Hershey Medical Center between June 3, 2018 and March 31, 2019. Limiting the data by anesthesia Current Procedural Terminology code and to complete cases with PONV risk and antiemetic interventions, we evaluated the performance of 83 anesthesia clinicians on 2,211 anesthesia cases. Our metric demonstrated considerable variance between clinicians in the adherence to risk-adjusted utilization of antiemetic interventions. Risk seemed to drive utilization only in few clinicians. We demonstrated the impact of social determinants of health on MIP, illustrating its utility for health science and disparity research. Conclusion The strength of our novel measure of individual clinician performance is its generalizability, as well as its intuitive graphical representation of risk-adjusted individual performance. However, accuracy, precision and validity, stability over time, sensitivity to system perturbations, and acceptance among clinicians remain to be evaluated.

Variability in Hospital Admission Rates for Neonates With Fever in North Carolina

Background. Despite multiple guidelines recommending admission, there is significant variation among emergency departments (EDs) regarding disposition of neonates presenting with fever. We performed a statewide epidemiologic analysis to identify characteristics that may influence patient disposition in such cases within North Carolina. Methods. This study is a retrospective cohort study of infants 1 to 28 days old with a diagnosis of fever presenting to North Carolina EDs from October 1, 2010, to September 30, 2015, using data from the NC DETECT (North Carolina Disease Event Tracking and Epidemiologic Collection Tool) database. We analyzed various patient epidemiology characteristics and their associations with patients being admitted or discharged from the emergency room setting. Results. Of 2745 unique patient visits for neonatal fever, 1173 (42.7%) were discharged from the ED, while 1572 (57.3%) were either admitted or transferred for presumed admission. Age, sex, region within North Carolina, and the presence of a pediatric service did not significantly influence disposition. An abnormal documented ED temperature was associated with higher likelihood of admission ( P < .01). The size of the hospital was also found to be significant when comparing large with small hospitals ( P < .01). Government-funded insurance was associated with lower likelihood of admission ( P < .01). Conclusions. A high number of neonates diagnosed with fever were discharged home, inconsistent with current recommendations. An association with a government-funded insurance represents a possible health care disparity. Further studies are warranted to further understand these variations in practice.